A bivalent remipede toxin promotes calcium release via ryanodine receptor activation
Michael J. Maxwell,
Chris Thekkedam,
Cedric Lamboley,
Yanni K.-Y. Chin,
Theo Crawford,
Jennifer J. Smith,
Junyu Liu,
Xinying Jia,
Irina Vetter,
Derek R. Laver,
Bradley S. Launikonis,
Angela Dulhunty,
Eivind A. B. Undheim () and
Mehdi Mobli ()
Additional contact information
Michael J. Maxwell: The University of Queensland
Chris Thekkedam: Australian National University
Cedric Lamboley: The University of Queensland
Yanni K.-Y. Chin: The University of Queensland
Theo Crawford: The University of Queensland
Jennifer J. Smith: The University of Queensland
Junyu Liu: The University of Queensland
Xinying Jia: The University of Queensland
Irina Vetter: The University of Queensland
Derek R. Laver: University of Newcastle
Bradley S. Launikonis: The University of Queensland
Angela Dulhunty: Australian National University
Eivind A. B. Undheim: The University of Queensland
Mehdi Mobli: The University of Queensland
Nature Communications, 2023, vol. 14, issue 1, 1-13
Abstract:
Abstract Multivalent ligands of ion channels have proven to be both very rare and highly valuable in yielding unique insights into channel structure and pharmacology. Here, we describe a bivalent peptide from the venom of Xibalbanus tulumensis, a troglobitic arthropod from the enigmatic class Remipedia, that causes persistent calcium release by activation of ion channels involved in muscle contraction. The high-resolution solution structure of φ-Xibalbin3-Xt3a reveals a tandem repeat arrangement of inhibitor-cysteine knot (ICK) domains previously only found in spider venoms. The individual repeats of Xt3a share sequence similarity with a family of scorpion toxins that target ryanodine receptors (RyR). Single-channel electrophysiology and quantification of released Ca2+ stores within skinned muscle fibers confirm Xt3a as a bivalent RyR modulator. Our results reveal convergent evolution of RyR targeting toxins in remipede and scorpion venoms, while the tandem-ICK repeat architecture is an evolutionary innovation that is convergent with toxins from spider venoms.
Date: 2023
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Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:14:y:2023:i:1:d:10.1038_s41467-023-36579-w
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DOI: 10.1038/s41467-023-36579-w
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